rs372149429

chr10-74985154-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_012330.4(KAT6B):c.2448G>A(p.Thr816=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000329 in 1,613,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00035 (0 hom.)
• Consequence: KAT6B NM_012330.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: -1.32

Genes affected

KAT6B (HGNC:17582): (lysine acetyltransferase 6B) The protein encoded by this gene is a histone acetyltransferase and component of the MOZ/MORF protein complex. In addition to its acetyltransferase activity, the encoded protein has transcriptional activation activity in its N-terminal end and transcriptional repression activity in its C-terminal end. This protein is necessary for RUNX2-dependent transcriptional activation and could be involved in brain development. Mutations have been found in patients with genitopatellar syndrome. A translocation of this gene and the CREBBP gene results in acute myeloid leukemias. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 10-74985154-G-A is Benign according to our data. Variant chr10-74985154-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 260235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.33 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000158 (24/152122) while in subpopulation NFE AF= 0.000294 (20/68016). AF 95% confidence interval is 0.000194. There are 0 homozygotes in gnomad4. There are 11 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KAT6B	NM_012330.4	c.2448G>A	p.Thr816=	synonymous_variant	12/18	ENST00000287239.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KAT6B	ENST00000287239.10	c.2448G>A	p.Thr816=	synonymous_variant	12/18	1	NM_012330.4	P2

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152122 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000155 AC: 39 AN: 251284 Hom.: 0 AF XY: 0.000162 AC XY: 22 AN XY: 135816

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000317

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000347 AC: 507 AN: 1461814 Hom.: 0 Cov.: 31 AF XY: 0.000330 AC XY: 240 AN XY: 727210

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.000268

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000433

Gnomad4 OTH exome AF: 0.000166

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152122 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74320

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000245 Hom.: 0

Bravo AF: 0.000159

EpiCase AF: 0.000382

EpiControl AF: 0.000296

ClinVar

Significance: Likely benign

Submissions summary: Benign:3 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1 Other:1

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 29, 2021	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Genitopatellar syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	9.2
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs372149429; hg19: chr10-76744912;